甲醛的遗传毒性及作用机制研究进展

甲醛是环境中普遍存在的一种有毒污染物,被国际癌症组织列为1类致癌物。甲醛在体内外均可造成DNA链断裂、染色体畸变和基因突变等遗传毒性。至今甲醛造成遗传毒性的机制尚不完全清楚,综合目前的研究结果可以发现,其可能主要通过两种途径产生遗传毒性,一是通过氧化应激及DNA加合、交联等直接作用致使遗传物质受到损伤而产生遗传毒性;二是通过抑制或干扰DNA的损伤修复而造成遗传毒性。为了更深入理解和研究甲醛的遗传毒性及其遗传毒性机制,该文就近年相关研究进展进行综述。     

医院污水对水环境毒理学风险的研究进展

医院污水作为水环境中毒性风险的主要来源之一,其毒性污染物质进入水环境后,会对水生生态平衡和饮用水水源造成潜在的负面影响。作者介绍了医院污水中对水环境造成毒性风险的主要污染物质和这些污染物在水环境中造成潜在毒性影响的研究状况与进展。     

有机氟杀鼠药中毒急救与护理体会

有机氟是一种烈性剧毒杀鼠药[1]。有氟乙酰胺,氟乙酸钠。固体有机氟白色无味,无臭针状结晶,易溶于水,口食性好,易造成误服,误服量大的特点。毒力强,俗称＂三步倒＂。挥发性强,其挥发性易造成周围食物吸收其毒性,成为带毒食物。其毒性和挥发性易造成连环中毒。如毒鼠→鼠死→鸡食死鼠而亡→人食死鸡中毒。食盐或糖吸收,其毒性成为带毒食物,人食中毒。不是现场发现很难诊断,多似精神症状,癫痫样出现。常误诊为怪病、癫痫、癔病、精神病等而误诊误治。     

全氟辛烷磺酸和全氟辛酸毒理学研究进展

全氟有机化合物,尤其是其代表性化合物全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)以及它们的盐类作为持久性有机环境污染物新成员,其所造成的全球性生态系统污染已成事实。本文以近年来国内外学者对PFOS和PFOA毒理学研究资料为依据,系统地阐述了PFOS和PFOA在实验动物和人体内的吸收、分布、排泄、代谢和毒物代谢动力学,以及它们对实验动物及人类可能造成的一般毒性、肝脏毒性、神经毒性、心血管毒性、胚胎发育与生殖毒性、遗传毒性与致癌性、免疫毒性等。同时指出,由于种属差异以及一些研究资料的尚不确定性,根据现有资料对PFOA和PFOS进行安全性评价的科学性值得商榷,进一步深入对PFOA和PFOS毒作用敏感指标及毒作用机制的探讨与研究,将成为今后环境科学和预防医学领域的研究重点。     

铂类抗肿瘤药物遗传毒性和生殖毒性的研究进展

以铂离子制剂为主的铂类抗肿瘤药物是目前应用最广的抗肿瘤药物之一,对卵巢癌、直肠癌等实体肿瘤有很好的疗效。但此类抗肿瘤药物可通过皮肤、呼吸道、肠道吸收等方式对人体造成潜在的生殖毒性、遗传毒性等健康损害。对铂类药物的结构、作用机制、生殖毒性和遗传毒性及相应的药物保护作用进行阐述,从基础动物实验等方面探究其毒性以及相应的预防措施现状,以期为后续职业暴露防护研究提供新的思维和探索方向。     

花粉枸杞对亚急性镉中毒拮抗作用

镉为己知半哀期长,易在人体内蓄积造成毒性损伤的重金属,肝肾是其重要的毒作用靶器官.     

有机磷杀虫剂的杂质与毒性

大部分有机磷杀虫剂的杂质会影响其毒性和药效。有机磷杀虫剂的杂质主要由其过剩的生产原料,化学合成(反应)的副产物和多余的有机溶剂等原因造成的。一般情况下,有机磷杀虫剂的杂质增加,其对哺乳动物的毒性增强,而杀虫剂药效下降。提高有机磷杀虫剂的纯度及质量,通常会降低毒性,增强药效,扩大其实际应用范围。     

甲基对硫磷慢性毒性研究进展

农药在农业发展中起着十分重要的作用,但农药残留危害健康,造成环境污染等问题也越来越受到人们的重视。甲基对硫磷(methyl parathion)是应用最为广泛的农药之一,具有毒性强、使用广泛且残留时间长等特征,它对人类健康造成的威胁越来越受重视。暴露于甲基对硫磷的人和动物会呈现多系统的损害,其毒性机制还在探索阶段。该文主要介绍了甲基对硫磷对神经系统、内分泌系统、免疫系统和生殖系统的慢性毒性。     

锰的神经兴奋毒性及其机制

锰作为机体必需微量元素之一，在体内可参与许多生物化学反应，但是过量锰进人体内则会引起锰中毒。以往人们对于锰神经毒性的研究多着眼于其造成的单胺类神经递质代谢及转运异常。而近年来，随着对神经兴奋毒性概念的提出及其研究的不断深入，发现神经兴奋毒性可能是慢性锰中毒发生、发展机制中的重要环节。本文将对锰的神经兴奋毒性及其作用机制作一综述。     

农药百草枯的急性毒性评价

目的评价百草枯的急性毒性特点,为中毒治疗提供参考依据。方法按国家标准《农药登记毒理学试验方法》（GB15670-1995）进行了小鼠急性经口毒性、豚鼠急性经皮毒性、家兔急性眼刺激性和家兔急性皮肤刺激性毒性试验研究。结果百草枯对雌、雄性小鼠急性经口LD50值分别为108.0 mg/kg.BW和126.0 mg/kg.BW,属中毒性。对雌、雄性豚鼠急性经皮LD50值分别为233.0 mg/kg.BW和200.0 mg/kg.BW,属中毒性。对家兔急性眼刺激性试验结果为轻度至中度刺激性,对家兔急性皮肤刺激性试验结果为中度刺激性。毒性特点为百草枯急性中毒可造成全身各器官组织的损伤,持续时间较长,恢复缓慢。结论百草枯毒性较大,可迅速吸收而造成多器官组织严重损害,中毒治疗应尽早采取有效的方法,全面保护和减轻中毒器官组织的损伤。     

Combined Effects of PFOS and PFOA on Zebrafish (Danio rerio) Embryos

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two kinds of emerging contaminants most studied in recent years. However, there is limited information about their combined toxicity to aquatic organisms. In the present study, the single and combined toxicity of PFOA and PFOS to zebrafish (Danio rerio) embryos were investigated. PFOS was more toxic than PFOA for the single toxicity. In four mixtures, PFOS and PFOA showed complex interactive effects that changed from additive to synergistic effect, then to antagonistic effect, and at last turnover to synergic effect again, with increased molar ratios of PFOS. Neither the concentration-addition model nor the independent-action model could predict the combined effects when strong interactive effects existed. Although the interactive effects of PFOS and PFOA affected their combined toxicity, the trend of mixture toxicity still showed an increase with increasing molar ratios of PFOS in the mixture.     

Partial life-cycle toxicity and bioconcentration modeling of perfluorooctanesulfonate in the northern leopard frog (Rana pipiens)

A number of recent monitoring studies have demonstrated elevated concentrations of perfluorooctanesulfonate (PFOS) in humans and wildlife throughout the world. Although no longer manufactured in the United States, the global distribution and relative persistence of PFOS indicates a need to understand its potential ecological effects. Presently, little is known concerning toxicity of PFOS in chronic exposures with aquatic species. Therefore, we evaluated the effects of PFOS on survival and development of the northern leopard frog (Rana pipiens) from early embryogenesis through complete metamorphosis. Exposures were conducted via water at measured PFOS concentrations ranging from 0.03 to 10 mg/L. Animals exposed to 10 mg/L began dying within approximately two weeks of test initiation. Survival was not affected by PFOS at lower concentrations; however, time to metamorphosis was delayed and growth reduced in the 3-mg/L treatment group. Tadpoles readily accumulated PFOS directly from water. Using a one-compartment bioaccumulation model, growth was shown to have a modest impact on steady-state PFOS concentrations. Variability in observed growth rates and the possible contribution of a size-dependent decrease in PFOS elimination rate contributed uncertainty to modeling efforts. Nevertheless, fitted uptake and elimination rate constants were comparable to those determined in earlier studies with juvenile rainbow trout. Overall, our studies suggest that R. pipiens is not exceptionally sensitive to PFOS in terms of either direct toxicity or bioconcentration potential of the chemical.     

Aquatic predicted no-effect-concentration derivation for perfluorooctane sulfonic acid

Perfluorooctane sulfonic acid (PFOS), a representative perfluorinated surfactant, is an anthropogenic pollutant detected in various environmental and biological matrices. Some laboratory and field work has been conducted to assess the aquatic toxicity of PFOS, but little is known regarding its toxicity threshold to the aquatic ecosystem. In the present study, predicted no-effect concentrations (PNECs) were derived by four different approaches. The interspecies correlation estimation (ICE) program and final acute-to-chronic ratio (FACR) were applied to the development of PNEC based on the toxic mode of action (MOA) of PFOS. By comparison of the different PNECs, the recommended aquatic toxicity thresholds for PFOS are in the range of 0.61 to 6.66?μg/L. Based on comparison of PNEC values, microcosm results, and reported environmental concentrations, PFOS appears not to pose a serious threat to aquatic organisms. The present results demonstrate that MOA is an important consideration for the derivation of reliable PNECs; moreover, the ICE-based species sensitivity distribution (SSD) method can be used to derive PNECs when toxicological data are limited. The application of MOA and ICE for deriving PNEC values in the present study may facilitate studies on using a combination of quantitative structure-activity relationship (QSAR) models and ICE to estimate PNECs.     

Phytotoxicity of PFOS and PFOA to Brassica chinensis in different Chinese soils

PFOS and PFOA are potential persistent organic pollutants that have raised many concerns in recent years. Research focusing on phytotoxicity of PFOS and PFOA to higher plants is necessary for their risk assessments. However, few toxicity data exist for PFOS or PFOA and higher plants. Here we investigated phytotoxicity of PFOS and PFOA to Brassica chinensis root growth in six different Chinese soils varying widely in soil properties using a standardized root length assay. The effective concentrations of added PFOS and PFOA causing 50% inhibition (EC₅₀) ranged from 95 to >200 mg kg⁻¹ for PFOS and from 107 to 246 mg kg⁻¹ for PFOA, respectively, representing more than 2.1- and 2.3-fold variation among the tested soils. Regressions of soil PFOS and PFOA toxicity threshold values (EC_x and NOECs) with various soil properties showed that the amount of organic matter was the most significant factor affecting their toxicity to B. chinensis.     

Chronic zebrafish PFOS exposure alters sex ratio and maternal related effects in F1 offspring

Perfluorooctanesulfonic acid (PFOS) is an organic contaminant ubiquitous in the environment, wildlife, and humans. Few studies have assessed its chronic toxicity on aquatic organisms. The present study defined the effects of long-term exposure to PFOS on zebrafish development and reproduction. Specifically, zebrafish at 8 h postfertilization (hpf) were exposed to PFOS at 0, 5, 50, and 250 μg/L for five months. Growth suppression was observed in the 250 μg/L PFOS-treated group. The sex ratio was altered, with a significant female dominance in the high-dose PFOS group. Male gonad development was also impaired in a dose-dependent manner by PFOS exposure. Although female fecundity was not impacted, the F1 embryos derived from high-dose exposed females paired with males without PFOS exposure developed severe deformity at early development stages and resulted in 100% larval mortality at 7 d postfertilization (dpf). Perfluorooctanesulfonic acid quantification in embryos indicated that decreased larval survival in F1 offspring was directly correlated to the PFOS body burden, and larval lethality was attributable to maternal transfer of PFOS to the eggs. Lower-dose parental PFOS exposure did not result in decreased F1 survival; however, the offspring displayed hyperactivity of basal swimming speed in a light-to-dark behavior assessment test. These findings demonstrate that chronic exposure to PFOS adversely impacts embryonic growth, reproduction, and subsequent offspring development.     

Toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid on freshwater macroinvertebrates (Daphnia magna and Moina macrocopa) and fish (Oryzias latipes)

Because of their global distribution, persistence, and tendency to bioaccumulate, concerns about perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are growing. We determined the toxicity of PFOS and PFOA in several freshwater organisms, including two cladocerans, Daphnia magna and Moina macrocopa, and the teleost Oryzias latipes. In general, PFOS is approximately 10 times more toxic than PFOA in these organisms. In M. macrocopa, the median lethal concentration (LC50) was 17.95 mg/L for PFOS and 199.51 mg/L for PFOA. Moina macrocopa exhibited greater sensitivity than D. magna to both perfluorinated compounds in both acute and chronic exposures. In the 48-h acute toxicity test, M. macrocopa was approximately two times more sensitive than D. magna. In the 7-d chronic toxicity test, M. macrocopa showed significant reproductive changes at 0.31 mg/L for PFOS, which was approximately seven times lower than the effect concentrations observed over the 21-d exposure in D. magna. Two-generation fish toxicity tests showed that parental exposure to both compounds affected the performance of offspring. Unexposed progeny-generation (F1) fish exhibited elevated mortality and histopathological changes that were correlated with exposure in the parental generation (F0). Continuous exposure from F0 through F1 generations increased the extent of adverse effects. Considering the persistent nature of PFOS and PFOA, more research is required to determine potential consequences of long-term exposure to these compounds in aquatic ecosystems.     

Toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid to Chironomus tentans

Two perfluorinated surfactants, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were evaluated for their toxicity to the aquatic midge, Chironomus tentans. Impetus for this laboratory study originated from a 10-d, in situ field assessment in which C. tentans was exposed to PFOS at concentrations ranging from 300 to 30,000 microg/L. No midges survived these exposures. Midge survival in a preliminary, acute 10-d laboratory test with nominal PFOS concentrations ranging from 0.1 to 100,000 microg/L showed similar toxicity with respect to survival (median lethal concentration [LC50], 45.2 microg/L) and growth (median effective concentration [EC50], 27.4 microg/L). A parallel test using PFOA indicated no significant impacts on survival or growth. A definitive 10-d assay with PFOS concentrations ranging from 1 to 150 microg/L produced an EC50 for growth (87.2+/-11.6 microg/L) of the same order of magnitude as that in the preliminary findings. The same was not true for survival, however, with the LC50 falling outside the range of test concentrations. To further investigate the sensitivity of C. tentans to PFOS, we conducted a chronic life-cycle test using a nominal concentration range of 1 to 100 microg/L. Three of the four endpoints measured-survival, growth, and emergence-were significantly affected, with EC50 values of 92.2+/-3.1, 93.8+/-2.6, and 94.5+/-3.2 microg/L, respectively. Reproduction was not affected by those PFOS concentrations at which females emerged. The results of the present study indicate that PFOS toxicity thresholds for C. tentans are as much as three orders of magnitude lower than those reported for other aquatic organisms but, at present, are approximately two orders of magnitude higher than those concentrations typically observed in aquatic environments.     

Impacts of two perfluorinated compounds (PFOS and PFOA) on human hepatoma cells: cytotoxicity but no genotoxicity?

Perfluorinated compounds (PFCs) and particularly two of them, perfluoroctanoate (PFOA) and perfluorooctanesulfonate (PFOS), have been widely produced and used since 1950. They both persist in the environment and accumulate in wildlife and humans. The toxicity of PFOS and PFOA has been studied extensively in rodents with several adverse effects mainly a hepatocarcinogenic potential. Carcinogenic effects are not highlighted in humans' studies. In this study, we investigated the cytotoxic and genotoxic effects of PFOA and PFOS using human HepG2 cells after 1 or 24h of exposure. The cytotoxic and genotoxic potential was evaluated by MTT assay, single cell gel electrophoresis (SCGE) assay and micronucleus assay respectively. We measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate to identify a potential mechanism of toxicity. We observed a cytotoxic effect of PFOA and PFOS after 24h of exposure starting from a concentration of 200 μM (MTT: -14.6%) and 300 μM (MTT: -51.2%) respectively. We did not observe an increase of DNA damage with the comet assay or micronucleus with the micronucleus assay after exposure to the two PFCs. After 24h of exposure, both PFOA and PFOS highlight a decrease of ROS generation (-5.9% to -23%). We did not find an effect after an hour of exposure. Our findings show that PFOA and PFOS exert a cytotoxic effect on the human cells line HepG2 but nor PFOA or PFOS could induce an increase of DNA damage (DNA strand breaks and micronucleus) or reactive oxygen species at the range concentration tested. Our results do not support that oxidative stress and DNA damage are relevant for potential adverse effects of PFOA and PFOS. These results tend to support epidemiological studies that do not show evidence of carcinogenicity.     

Chronic PFOS Exposure Disrupts Thyroid Structure and Function in Zebrafish

Perfluorooctane sulfonic acid (PFOS), as a potential endocrine disrupting chemical, is widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on thyroid in aquatic organisms and the underlying mechanisms are largely unknown. The present study assessed the effect of chronic PFOS exposure on thyroid structure and function using zebrafish model. Zebrafish at 8 h post fertilization (hpf) were exposed to PFOS (250 µg/l) until 120 d post fertilization (dpf). Thyroid hormone (T₃ and T₄) level, thyroid morphology and thyroid function related gene expression were evaluated in zebrafish at 120 dpf. Our findings demonstrated that chronic PFOS exposure altered thyroid hormone level, thyroid follicular cell structure and thyroid hormone related gene expression, suggesting the validity of zebrafish as an alternative model for PFOS chronic toxicity screening.